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J C Griffiths

Publications and source records attributed to J C Griffiths.

At least 37 records · Page 2Linked to original sources
PubMed1985

Relevance of the pharmacology of oral tegafur to its use as a 5-FU pro-drug.

We have studied the pharmacology of iv and oral tegafur (FT) and compared the results with similar studies using continuously infused 5-FU. All patients received daily abdominal irradiation as well as FT. In eight patients receiving 1.0 g/m2 of iv FT, serum FT levels were essentially the same as those in five patients receiving the same dose of oral FT. Oral FT appeared well-absorbed, even with abdominal irradiation. The mean serum FT achieved on a daily basis was a linear function of the oral FT dose between 1.0 and 2.5 g/m2 and was consistently about 1000-fold higher than the resultant 5-FU level. The major FT metabolite, dehydro-FT (DHFT), was persistently present at about ten times the 5-FU level. Because of their long half-lives, both FT and DHFT accumulate during continuous therapy. When the mean serum 5-FU levels with oral FT were compared to those found during continuous 5-FU infusions, we found that oral FT was the equivalent of low-level 5-FU infusion. Oral FT at 1.0 g/m2 was the equivalent of about 11.5 mg/kg/24 hours of 5-FU, increasing to about 17.5 mg/kg of 5-FU for oral FT at 2.5 g/m2. The pharmacologic properties of FT appear to dictate its most useful schedule (continuous oral dosing in multiple doses) and explain why FT alone is not ideal as a 5-FU pro-drug. In addition, insight into the pharmacokinetic limitations of FT also suggests means by which its usage may be improved, including its potential application as a radiosensitizer.

Administration, Oral↗
PubMed1983

Bone marrow pressure changes under an inflatable tourniquet.

Theoretical calculations suggest that under a limb tourniquet, the pressure at the bone/tissue interface is greater than it is more peripherally. The central bony core must be incompressible for this hypothesis to be correct. Experiments designed to measure the intramedullary pressure confirm that this pressure does not rise at tourniquet pressures above the systolic blood pressure. It has also been suggested that shear stresses are the most likely cause of nerve damage under a tourniquet but this depends on the conversion of the tissue under compression into a fibro-elastic solid. This is likely to occur when all fluid has been driven out. From the experiments such a fluid shift does not seen to occur via the intramedullary cavity but it must nevertheless occur at an early stage of rising tourniquet pressure, probably by fluid shift through the veins proximal and distal to the tourniquet.

Arm↗
PubMed1983

The laboratory diagnosis of prostatic adenocarcinoma.

At the close of each decade, we are reminded by medical statisticians that our longevity increases significantly. For the male, especially if he be of black race this statement has an ironic twist. Over age 70, prostatic "cancer" assumes the leadership list of "cancers" in general, supplanting lung and colo-rectal. One interesting point evolved by careful autopsy studies suggests that this incidence is found coincidentally and is not primarily responsible for the cause of death. This illustrates a different significance to other neoplasia, and offers useful opportunities to study the evolution of a neoplasm. In contrast to other "cancers" (for example pulmonary), the histological nature of the tumor is almost totally derived from the acinar lobules and designated adenocarcinoma. Neoplasia arising from the fibromuscular stroma (sarcoma) and metaplastic ductus (squamous cell carcinoma) constitute less than 1% of all prostate cancers. Histological appearances, however, are not as simple as hoped. As in many tumors the section may present a uniform well-differentiated adenocarcinoma in which the acinar structure is well maintained--yet at the opposing end of the spectrum show a fatally dedifferentiated picture whose organ origin is difficult to determine. Adding to the complication is the wide variation, far more commonly seen, of the mixed tumor with all variations presenting a composite panorama of histology. Indeed the pure type is rare. As with all neoplastic disease, early detection is critical, since opportunity for cure with the various forms of therapy from surgery through radiation to chemotherapy are increasing rapidly. The prostate gland is relatively accessible to the trained finger of the physician and later stages of the disease are palpable. However, the earliest Stage (I) is not discovered by rectal examination, hence provides an ideal opportunity for the serum tumor marker, to identify disease. Since 1938, disseminated prostatic adenocarcinoma has been associated with elevation of activity of an enzyme acid phosphatase. Although there are several isoenzymes the prostatic specific one has in the past been assayed by different spectrophotometric techniques using selective substrate and chemical inhibition. More recently various immunological methods have added a greater sensitivity and specificity to the early detection of prostatic adenocarcinoma. However is should be clearly stated that prostatic acid phosphatase is not cancer specific and can be associated with other nonmalignant lesions in the prostate gland.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1982

Clearance of continuously infused 5-fluorouracil in adults having lung or gastrointestinal carcinoma with or without hepatic metastases.

The steady-state apparent total body clearances (TBC) of continuously infused 5-fluorouracil (5-FU) were determined in 16 adult male patients who were receiving combined 5-FU-radiation therapy. Seven patients (group A) had Stage III adenocarcinoma or epidermoid lung carcinomas; none had known metastases. Five patients had gastrointestinal carcinomas (group B), without known hepatic metastases. Four had gastrointestinal carcinomas with evidence of hepatic metastases (group C). TBCs were calculated from infusion rates and serum 5-FU concentration data. The means (standard errors) of the TBCs were: group A, 4.49 (0.53); group B, 6.51 (0.53); group C, 2.96 (0.91) L/kg/h. The difference among the means was found to be significant (p less than 0.002) by one-way ANOVA. Differences among the groups were then examined using 95 percent confidence intervals: group A was not different from group B or group C; however, groups B and C differed from each other. Patients with hepatic metastases have 5-FU TBCs about half that of those found in patients without hepatic involvement. Clinically, patients in group C attained the higher serum 5-FU concentrations known to be radiosensitizing more frequently than patients in the other two groups; differences in toxicity were not evident. This suggests that administration of an agent that can compete with 5-FU for hepatic metabolism to patients with rapid clearance might improve the therapeutic efficacy of 5-FU.

Adult↗
PubMed1981

Alterations of peripheral blood B-lymphocyte populations in plasma cell disorders.

Peripheral blood lymphocytes of patients with multiple myeloma, macroglobulinemia, and monoclonal gammopathy of uncertain significance were analyzed for B cells, and cells bearing kappa light chains and lambda light chains on their surfaces. Compared with controls, the number of B cells were decreased in all three groups. Contrary to other reports, the authors found a B-cell depression of similar magnitude in patients with untreated myeloma and in those with apparently benign monoclonal gammopathy. There was no difference between treated and untreated myeloma patients as a group, or as individuals studied before and after treatment. However, in comparison to control patients, alkylator therapy depressed the leukocyte count, lymphocyte count, and B-cell number both in the myeloma and in the macroglobulinemia groups. All five patients with previously untreated macroglobulinemia had an increased proportion of circulating lymphocytes with surface light chains of the same type as the M protein. Two patients with IgG myeloma-like disorders had increased circulating B cells with monoclonal surface light chains. This study supports the concepts that normal B cells are depressed in plasma cell disorders, and that abnormal B cells, which are apparently monoclonal, do circulate in some cases. Our results are compared with other published data.

Aged↗
PubMed1981

Improved liquid chromatographic assay for serum fluorouracil concentrations in the presence of ftorafur.

An improved liquid chromatographic assay for serum ftorafur and fluorouracil is shown to be routine, sensitive, and reproducible using 200 micro l of serum. Dilute ammonium acetate buffer at pH 10.2 is used for solubilization of the evaporated ethyl acetate extract for injection into the liquid chromatograph. A stability study indicated little or no in vitro formation of fluorouracil from ftorafur under the conditions described. Low serum fluorouracil levels were found after administration of therapeutic doses of ftorafur.

Chromatography, Liquid↗
PubMed1980

Clinical applications of the paraplegic swivel walker.

An account is given of ten years experience of swivel walkers in 135 paraplegics of all ages and types. The majority of patients were victims of spinal bifida. Reference is made to the importance of engineering design and proper maintenance of the orthosis. The degree to which the device is utilized is discussed and the particular value it has in young children is stressed. Further developments, especially those which satisfy the increasing demand for the device for adult use are mentioned, notably those needed to simplify the problems of transfer into and from the device.

Adolescent↗
PubMed1980

Human T cell antigens defined by monoclonal antibodies: the 65,000-dalton antigen of T cells (T65) is also found on chronic lymphocytic leukemia cells bearing surface immunoglobulin.

Peripheral blood lymphocytes from 15 patients with chronic lymphocytic leukemia (CLL), four patients with lymphosarcoma cell leukemia (LCL), four patients with hairy cell leukemia, and three patients with a monoclonal gammopathy (two with IgM, one with IgA) were tested for reactivity with the anti-T cell monoclonal antibody, T101. By immunofluorescent staining, all of the patients had circulating monoclonal surface Ig+ (sIg+) lymphocytes except for three CLL patients whose leukemia cells were sIg-. The leukemia cells of all of the sIg+ CLL cases were reactive with T101 antibody by indirect immunofluorescence; however, the abnormal cells in all of the remaining cases were unreactive. Reactivity of sIg+ CLL cells with T101 was confirmed by a radioactive binding assay, absorption analysis, and complement-dependent cytotoxicity. Moreover, a 65,000-dalton protein (T65), similar to that found on T cells, was precipitated by T101 antibody from the surface of sIg+ CLL cells. The fluorescent staining of sIg+ CLL cells by T101 antibody was weak as was the staining of the sIg. This was in contrast to the LCL cells, which had intense staining sIg and absence of staining with T101 antibody. These data demonstrate the existence of two major subtypes of CLL that have phenotypes sIg+ and T101+ and sIg-T101-. The implication of the finding of dual T and B markers on the major type of CLL, but not other B cell malignancies is discussed.

Absorption↗
PubMed1980

Prostate-specific acid phosphatase: re-evaluation of radioimmunoassay in diagnosing prostatic disease.

The availability of a radioimmunoassay for prostate-specific acid phosphatase has allowed a correlative study between this technique and conventional colorimetric assays in the four clinical stages of prostatic adenocarcinoma. Results of such a study show an increased diagnostic sensitivity of the radioimmunoassay in all stages, but in 14% of Stage IV adenocarcinomas there was no increase in prostatic acid phosphatase above the ranges ordinarily expected for all methods. In cases of benign prostatic hyperplasia, there was an increase associated with in vivo tissue cytolysis, comparable to Stage II and III adenocarcinoma. The sensitivity of the test in Stage I is still low, but testing for combinations of tumor markers might increase the diagnostic yield. Conversely, a different clinical approach might be to establish baseline values in the "at-risk" patient, followed by regular determinations of prostate-specific acid phosphatase activity. Increases in activity within the normal expected range may be interpreted by the clinician as a herald of disease.

Acid Phosphatase↗
PubMed1979

A gas chromatographic mass spectrometric chemical ionization assay for haloperidol with selected ion monitoring.

A new gas chromatographic mass spectrometric chemical ionization assay for haloperidol with selectedion monitoring is presented which provides for better combined selectivity and sensitivity than previous assays. Levels of haloperidol in 2 ml of human plasma were reproducibly measured down to subnanogram levels. Both methane and methane--ammonia chemical ionization spectra are presented for haloperidol and the internal standard trifluperidol.

Adolescent↗